((2S,4R)-4,6-dihydroxytetrahydro-2H-pyran-2-yl)methyl carboxylate is a possible intermediate in the synthesis of statins. Statins, the representative examples of which may be selected from rosuvastatin, cerivastatin, atorvastatin, fluvastatin, pitavastatin, bervastatin, dalvastatin or their analogs or pravastatin, simvastatin, lovastatin or their analogs share a characteristic structure defined by respectively a heptenoic or heptanoic acid moiety (free acid, salt or lactone) connected to the aromatic or alicyclic core. Biological activity of statins is closely related to their stereochemistry, especially configuration at the chiral atoms of said heptenoic or heptanoic acid moiety.
In WO 2006/134482, a 2-deoxyribose-5-phophate aldolase (DERA) catalyzed aldol addition step is included in a process for forming atorvastatin.
JP 2005229858 discloses a method for producing ((4R,6S)-4,6 dihydroxytetrahydro-2-pyrone, wherein benzyloxyacetaldehyde is reacted with acetaldehyde in the presence of DERA. The reaction time of the enzymatic catalysis was 12 h.
WO 05/118794 deals with an improvement of the DERA enzyme. The isolated mutant enzymes may be used for the preparation of a 2,4-dideoxyhexose or a 2,4,6 trideoxyhexose having a high variety of substituents.
A DERA mutant was described catalyzing stereospecific aldol reaction (Tetrahedron Letters 2004, 45, 2439-2441). The DERA mutant showed a relative improvement in catalytic activity, and thus improved yields compared with the wild type DERA. The reaction time of the enzymatic catalysis was 6 days. One product obtained from this enzymatic catalysis was proposed for the synthesis of atorvastatin.
A DERA for catalyzing stereospecific aldol reaction was further described in Proc. Nat. Acad. Sci. USA 2004, 101 (16) 5788-5793, showing improved volumetric productivity of the enzymatic process. The inhibitory effects of the substrates used towards enzyme activity are also described. The reaction time of the enzymatic catalysis was 3 h. The products obtained from this enzymatic catalysis were proposed for the synthesis of atorvastatin or rosuvastatin
A stereospecific aldol reaction with three aldehyde substrates catalyzed by 2-deoxyribose-5-phophate aldolase (DERA) does not equally accept all substituted acetaldehydes as substrates for DERA (Am. Chem. Soc.; 117, 29, (1995) pp 7585) and certain substrates show inhibitory effects on DERA activity. The reaction time of the enzymatic catalysis was 6 days.
In WO 2007/039287 A1, a synthesis of lactonized statin side chains intermediate VI via iodolactone synthesis is described, which requires 6 organic synthetic steps. In this multiple step synthesis, the 4th step is a lactone forming step defining the stereochemistry of the iodolactone intermediate product. This lactone forming step provides relatively low stereoselectivity only. Some reagents used in stoichiometric amount like the I-compounds, the Ag-compound, the Grignard reagent and the enantiopure starting compound are quite expensive. The 6 steps of organic synthesis (shown in the following) gave a total yield of 19%:

The object of the present invention is to provide intermediate compounds and processes as building blocks for effectively producing statins.